tbuckley/cabot-search huggingface dataset:
Predicting Moral Elevation Conveyed in Danmaku Comments Using EEGs
Authors: Chenhao Bao, Xin Hu, Dan Zhang, Zhao Lv, Jingjing Chen
Journal: Cyborg and Bionic Systems (2023)

Moral elevation, the emotion that arises when individuals observe others' moral behaviors, plays an important role in determining moral behaviors in real life. While recent research has demonstrated the potential to decode basic emotions with brain signals, there has been limited exploration of affective computing for moral elevation, an emotion related to social cognition. To address this gap, we recorded electroencephalography (EEG) signals from 23 participants while they viewed videos that were expected to elicit moral elevation. More than 30,000 danmaku comments were extracted as a crowdsourcing tagging method to label moral elevation continuously at a 1-s temporal resolution. Then, by employing power spectra features and the least absolute shrinkage and selection operator regularized regression analyses, we achieved a promising prediction performance for moral elevation (prediction r = 0.44 ± 0.11). Our findings indicate that it is possible to decode moral elevation using EEG signals. Moreover, the small-sample neural data can predict the continuous moral elevation experience conveyed in danmaku comments from a large population.
Metabolic challenges and interventions in CAR T cell therapy
Authors: Jhan-Jie Peng, Limei Wang, Zhiyu Li, Cheng-Lung Ku, Ping-Chih Ho
Journal: Science Immunology (2023)

Chimeric antigen receptor (CAR) T cells have achieved true clinical success in treating hematological malignancy patients, laying the foundation of CAR T cells as a new pillar of cancer therapy. Although these promising effects have generated strong interest in expanding the treatment of CAR T cells to solid tumors, reproducible demonstration of clinical efficacy in the setting of solid tumors has remained challenging to date. Here, we review how metabolic stress and signaling in the tumor microenvironment, including intrinsic determinants of response to CAR T cell therapy and extrinsic obstacles, restrict the efficacy of CAR T cell therapy in cancer treatment. In addition, we discuss the use of novel approaches to target and rewire metabolic programming for CAR T cell manufacturing. Last, we summarize strategies that aim to improve the metabolic adaptability of CAR T cells to enhance their potency in mounting antitumor responses and survival within the tumor microenvironment.
Blockade of VEGFR3 signaling leads to functional impairment of dural lymphatic vessels without affecting autoimmune neuroinflammation
Authors: Zhilin Li, Salli Antila, Harri Nurmi, Dmitri Chilov, Emilia A. Korhonen, Shentong Fang, Sinem Karaman, Britta Engelhardt, Kari Alitalo
Journal: Science Immunology (2023)

The recent discovery of lymphatic vessels (LVs) in the dura mater, the outermost layer of meninges around the central nervous system (CNS), has opened a possibility for the development of alternative therapeutics for CNS disorders. The vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential for the development and maintenance of dural LVs. However, its significance in mediating dural lymphatic function in CNS autoimmunity is unclear. We show that inhibition of the VEGF-C/VEGFR3 signaling pathway using a monoclonal VEGFR3-blocking antibody, a soluble VEGF-C/D trap, or deletion of the Vegfr3 gene in adult lymphatic endothelium causes notable regression and functional impairment of dural LVs but has no effect on the development of CNS autoimmunity in mice. During autoimmune neuroinflammation, the dura mater was only minimally affected, and neuroinflammation-induced helper T (T H ) cell recruitment, activation, and polarization were significantly less pronounced in the dura mater than in the CNS. In support of this notion, during autoimmune neuroinflammation, blood vascular endothelial cells in the cranial and spinal dura expressed lower levels of cell adhesion molecules and chemokines, and antigen-presenting cells (i.e., macrophages and dendritic cells) had lower expression of chemokines, MHC class II–associated molecules, and costimulatory molecules than their counterparts in the brain and spinal cord, respectively. The significantly weaker T H cell responses in the dura mater may explain why dural LVs do not contribute directly to CNS autoimmunity.
Correction: Effects of a WHO-guided digital health intervention for depression in Syrian refugees in Lebanon: A randomized controlled trial
Authors: Pim Cuijpers, Eva Heim, Jinane Abi Ramia, Sebastian Burchert, Kenneth Carswell, Ilja Cornelisz, Christine Knaevelsrud, Philip Noun, Chris van Klaveren, Edith van’t Hof, Edwina Zoghbi, Mark van Ommeren, Rabih El Chammay
Journal: PLoS Medicine (2023)

[This corrects the article DOI: 10.1371/journal.pmed.1004025.].
Table of Contents
Authors: J De Wilt, S Bach, L Hendriks, K Kerr, J Menis, T Mok, U Nestle, A Passaro, S Peters, D Planchard, E Smit, B Solomon, G Veronesi, M Reck, G Lopes, B Cho, D Kowalski, K Kasahara, Y.-L Wu, G De Castro, H Turna, R Cristescu, D Aurora-Garg, A Loboda, J Lunceford, J Kobie, M Ayers, M Pietanza, B Piperdi, R Herbst, A Bayle, L Belcaid, M Aldea, D Vasseur, F Peyraud, C Nicotra, A Geraud, M Sakkal, L Seknazi, L Cerbone, F Blanc-Durand, J Hadoux, F Mosele, M Tagliamento, A Bernard-Tessier, B Verret, C Smolenschi, R Clodion, N Auger, P Romano, A Gazzah, M Camus, J Micol, O Caron, A Hollebecque, Y Loriot, B Besse, L Lacroix, E Rouleau, S Ponce, J Soria, F Barlesi, F Andre
Journal: Annals of Oncology (2023)
Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2− early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2− trial
Authors: O. Gluz, S. Kuemmel, U. Nitz, M. Braun, K. Lüdtke-Heckenkamp, R. von Schumann, M. Darsow, H. Forstbauer, J. Potenberg, C. Uleer, E.M. Grischke, B. Aktas, C. Schumacher, C. zu Eulenburg, R. Kates, K. Jóźwiak, M. Graeser, R. Wuerstlein, R. Baehner, M. Christgen, H.H. Kreipe, N. Harbeck
Journal: Annals of Oncology (2023)
Assessment of dupilumab in children with moderate‐to‐severe type 2 asthma with or without evidence of allergic asthma
Authors: Nikolaos G. Papadopoulos, Stanley J. Szefler, Leonard B. Bacharier, Jorge F. Maspero, Christian Domingo, Alessandro Fiocchi, Jason K. Lee, Nadia Daizadeh, David J. Lederer, Megan Hardin, Rebecca Gall, Michel Djandji, Shahid Siddiqui, Juby A. Jacob‐Nara, Yamo Deniz, Paul J. Rowe
Journal: Allergy (2023)

Cytokines, such as interleukins (IL)-4/5/13, play a key role in multiple type 2 inflammatory diseases, including allergic asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In this post hoc analysis of VOYAGE (NCT02948959), dupilumab efficacy was evaluated in patients aged 6-11 years with type 2 asthma with or without evidence of allergic asthma (baseline serum total IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L).
Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland
Authors: Chris Robertson, Steven Kerr, Aziz Sheikh
Journal: The Lancet Regional Health - Europe (2023)

To the Editor:The BA.5 sub-lineage was first detected in South Africa in January 2022. 1 It was designated a variant of concern by the UK Health and Security Agency on May 18, 2022, and became dominant in the UK by June 24, 2022. 2 There are few longitudinal population-based studies on the risks of infection and serious COVID-19 outcomes of BA.5.A case control and cross-sectional study in Denmark found that BA.5 was associated with an increased risk of COVID-19 hospitalisation compared to BA.2. 3 A test negative case-control study in England found no evidence of reduced vaccine effectiveness (VE) against hospitalisation for BA.5 compared to BA.2. 4 In this study, we analysed severity of the BA.5 variant compared to BA.2, which was the most recent dominant Omicron sub-lineage in the UK prior to BA.5. 5 The Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform comprises of linked primary care, vaccination, reverse transcriptase polymerase chain reaction (RT-PCR), viralsequencing, hospitalisation and mortality data on 5.4 million (99% of the population).][8] COVID-19 hospitalisation was defined as hospital admission with an International Classification of Diseases (ICD)-10 codes for COVID-19 and with an RT-PCR positive test for SARS-CoV-2 within the 28 days prior to admission, or 2 days after admission.COVID-19 death was defined as death with ICD-10 codes for COVID-19 on the death certificate within a 56 day follow up from the test date.We undertook cohort and matched analyses investigating risk of COVID-19 hospitalisation and death associated with BA.5 compared to BA.2 using EAVE II.The study start date was April 1, 2022, and the study end was September 30, 2022.In all analyses, for the event that was being studied as the dependent variable, we used the first event that occurred in the study period, and we restricted to the subset of individuals that were virologically-sequenced with the BA.2 or BA.5 variants and who were not in hospital at the time the specimen
Evaluation of quality of life (QOL) of young patients with primary hyperhidrosis (PH) before and after endoscopic thoracic sympathectomy (ETS)
Authors: Sonia Oliveira Lima, José Machado Neto, Letícia Moreira Fontes, Maria Bernadete Galrão de Almeida Figueiredo, Jéssica Macêdo Santos, Vanessa Rocha Santana
Journal: Journal of the American Academy of Dermatology (2023)
Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial
Authors: Vivek Subbiah, Robert J. Kreitman, Zev A. Wainberg, Anas Gazzah, Ulrik Lassen, Alexander Stein, Patrick Y. Wen, Sascha Dietrich, Maja J. A. de Jonge, Jean-Yves Blay, Antoine Italiano, Kan Yonemori, Daniel C. Cho, Filip Y. F. L. de Vos, Philippe Moreau, Elena Elez Fernandez, Jan H. M. Schellens, Christoph C. Zielinski, Suman Redhu, Aislyn Boran, Vanessa Q. Passos, Palanichamy Ilankumaran, Yung-Jue Bang
Journal: Nature Medicine (2023)

Abstract BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E -mutated advanced rare cancers: anaplastic thyroid carcinoma ( n = 36), biliary tract cancer ( n = 43), gastrointestinal stromal tumor ( n = 1), adenocarcinoma of the small intestine ( n = 3), low-grade glioma ( n = 13), high-grade glioma ( n = 45), hairy cell leukemia ( n = 55) and multiple myeloma ( n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E -mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .
Concerns about the Burden of Proof studies
Authors: Andrea J. Glenn, Xiao Gu, Frank B. Hu, Molin Wang, Walter C. Willett
Journal: Nature Medicine (2023)

We read with interest the Burden of Proof (BoP) studies [1][2][3][4][5] in which the authors conducted meta-analyses of epidemiological studies to provide an overall conservative quantitative assessment for several important public health questions.For ease of interpretation, they transformed the overall assessment into a star rating (1-5 stars).Examples include five stars for smoking and lung cancer, two stars for low vegetable intake and ischemic heart disease (IHD) and two stars for unprocessed red meat and type 2 diabetes (T2D), colorectal cancer and IHD 6 .They used this same method to assign just three stars to smoking in relation to IHD and one or two stars to other well-established relationships [1][2][3][4] .However, we believe there are serious methodological issues with their meta-analyses 5 ; the star rating of evidence strength is overly simplistic and could cast doubt on existing recommendations and policies intended to prevent chronic disease and treat illnesses.In the BoP analyses, the estimated uncertainty intervals (UIs) were several times wider than the 95% confidence intervals (CIs) generated by existing methods that account for heterogeneity among methods 7 .As an example of the BoP analyses 1 , for unprocessed red meat and T2D 15 studies were included in the meta-analysis, many of which were large and without evidence of small study bias.With what the authors described as a conventional analysis, there is a highly statistically significant and approximately linear positive association and the relative risk for 100 g per day of red meat intake versus no consumption was approximately 1.24.However, due to an
Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight
Authors: Song-Yang Zhang, Kyla Bruce, Zahra Danaei, Rosa J.W. Li, Daniel R. Barros, Rachel Kuah, Yu-Mi Lim, Laura H. Mariani, David Z. Cherney, Jennifer F.M. Chiu, Heather N. Reich, Tony K.T. Lam
Journal: Cell Metabolism (2023)
Pleiotropic and multi-systemic actions of physical exercise on PGC-1α signaling during the aging process
Authors: Ivo Vieira de Sousa Neto, Ana Paula Pinto, Vitor Rosetto Muñoz, Rita de Cássia Marqueti, José Rodrigo Pauli, Eduardo Rochete Ropelle, Adelino Sanchez Ramos da Silva
Journal: Ageing Research Reviews (2023)
Abstract LB232: Targeting MEK activity in pancreatic tumors resistant to the combination of 5FU, irinotecan, and oxaliplatin promotes response to immunotherapy
Authors: Thao D. Pham, Anastasia E. Metropulos, Nida Mubin, Dhavan N. Shah, Christina Spaulding, Mario Shields, David J. Bentrem, Hidayatullah G. Munshi
Journal: Cancer Research (2023)

Abstract FOLFIRINOX, a chemotherapy regimen consisting of 5FU, Leucovorin, Irinotecan, and Oxaliplatin, has been a first-line standard of care for patients with pancreatic adenocarcinoma (PDAC) for the last decade. However, low patient survival rates following treatment highlight frequent occurrence of resistance. Hence there is increasing interest in developing appropriate models of FOLFIRINOX resistance to identify subsequent line therapies. We have generated PDAC cell lines that exhibit acquired resistance to a combination of 5FU (F), Irinotecan (I), and Oxaliplatin (O) (FIO) in vitro. In mice, they form tumors that resemble FOLFIRINOX neoadjuvant-treated PDAC patients in regard to immune cell infiltration and a lack of response to single-agent anti-PD-1 therapy. We also show that similar to human PDAC tumors treated with neoadjuvant FOLFIRINOX, FIO-resistant tumors exhibit increased ERK1/2 phosphorylation. We demonstrate that the MEK inhibitor Trametinib reprograms the FIO-resistant tumors, but not the parental tumors, towards a less immunosuppressive tumor immune microenvironment. Importantly, Trametinib sensitizes FIO-resistant tumors to anti-PD-1 therapy, with the combination treatment significantly enhancing the cytolytic activity of the infiltrating CD8 + T cells and increasing tumor cell death. Taken together, our findings identify enhanced MEK/ERK signaling as a therapeutic target in FOLFIRINOX-resistant PDAC tumors, and suggest evaluating the combination of Trametinib and anti-PD-1 therapy in patients who progress on FOLFIRINOX. Citation Format: Thao D. Pham, Anastasia E. Metropulos, Nida Mubin, Dhavan N. Shah, Christina Spaulding, Mario Shields, David J. Bentrem, Hidayatullah G. Munshi. Targeting MEK activity in pancreatic tumors resistant to the combination of 5FU, irinotecan, and oxaliplatin promotes response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB232.
Abstract LB233: Preclinical analysis identifies predictive biomarker and potential pathways of resistance to lurbinectedin treatment in small cell lung cancer
Authors: Subhamoy Chakraborty, Charles Coleman, Deniz Demircioglu, Dan Hasson, Triparna Sen
Journal: Cancer Research (2023)

Abstract Background: Small cell lung cancer (SCLC) is an exceptionally aggressive disease with limited treatment options that typically result in transient responses. SCLC is responsible for approximately 250,000 deaths globally per year. Major hurdles to improving SCLC treatment include the development of rapid chemo-resistance and limited second-line therapies. Lurbinectedin is FDA approved as a second-line treatment for SCLC but shows a response in a subset of patients. Therefore, improved mechanistic understanding and identifying predictive biomarkers of lurbinectedin treatment is a major unmet clinical need. Methods: We treated SCLC cell lines and patient-derived xenograft (PDX) models from all major SCLC subtypes with lurbinectedin. Lurbinectedin-mediated changes in signaling pathways were studied by bulk RNA sequencing, western blot, and flow cytometry. Anti-tumor efficacy and toxicity studies were performed in vivo. Result: All human and PDX-derived SCLC cell lines showed sensitivity to lurbinectedin at a nano-molar concentration ranging from 1.905 to 30 nM. Bulk RNA-seq analysis showed lurbinectedin induced changes in neuroendocrine phenotype, DNA damage response and tumor progression markers in vitro. Single agent treatment of lurbinectedin showed remarkable anti-tumor efficacy in an ASCL1-driven PDX model. RNA sequencing analysis identified modulation of genes in multiple signaling pathways including PI3K-AKT, apoptosis and EMT to be significantly associated with the lurbinectedin response in PDX models. Conclusion: There is an immediate need to understand the subsets of SCLC that would be most sensitive to lurbinectedin and identify predictive biomarkers. We demonstrate MYC as a predictive biomarker for lurbinectedin response. We are the first to show that single agent lurbinectedin shows remarkable anti-tumor efficacy in a ASCL1-driven PDX models of SCLC. Furthermore, our pre and post-lurbinectedin treatment transcriptomic analysis identify the pathways that may contribute to primary or acquired resistance to lurbinectedin in SCLC. Finally, we identity candidate targets that would guide the design of future combination clinical trials with lurbinectedin in SCLC. Citation Format: Subhamoy Chakraborty, Charles Coleman, Deniz Demircioglu, Dan Hasson, Triparna Sen. Preclinical analysis identifies predictive biomarker and potential pathways of resistance to lurbinectedin treatment in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB233.
Abstract LB130: Single-cell multiomics analysis of myelodysplastic syndrome predicts clinical response to DNA methylation inhibitor therapy
Authors: Ignacio Campillo-Marcos, Marta Casado-Pelaez, Veronica Davalos, Gerardo Ferrer, Caterina Mata, Elisabetta Mereu, David Valcarcel, Antonieta Molero, Lurdes Zamora, Laura Palomo, Pamela Acha, Ana Manzanares, Francesc Solé, Manel Esteller
Journal: Cancer Research (2023)

Abstract Epigenetic alterations, such as DNA methylation aberrations, are a hallmark of human cancer. This observation has led to the assessment of hypomethylating agents (HMAs) as potential drugs to treat oncological patients, being considered the clinical approval of these pharmacological compounds in the therapy of myeloid malignancies as one of the main achievements of this scientific field. A good example is myelodysplastic syndrome (MDS), a pre-leukemia disorder that can evolve into acute myeloid leukemia (AML), where very few therapeutic options were available until the introduction of HMAs. However, it remains unsolved how we can predict if an MDS patient will response or not to the epigenetic drug and for how long. Using the great analytical power of the newly developed single-cell technologies, we have herein tackled this issue. To study the evolution of the clonal molecular and cellular architecture MDS upon the treatment with HMAs, we performed single-cell DNA sequencing (scDNA-seq) of an amplicon panel for 53 genes commonly mutated in myeloid malignancies and single-cell protein sequencing (scProt-seq) of 45 cell-surface proteins to provide a simultaneous landscape of the genetic setting and immunophenotype. We sequenced hundreds of thousands of cells from these MDS patients where paired bone marrow samples were obtained at the time of diagnosis and at the end of at least six cycles of azacitidine treatment. Our study has unveiled that the co-occurrence of particular truncating or stop codon mutations in the same myeloid progenitor cell; the multibranched dynamics of the mutant clones; and the persistence of particular cell lineages with distinct mutational profiles (such as non-classical monocytes and CD8+ effector T-cells) can predict the clinical response of MDS patients to HMA therapy. Citation Format: Ignacio Campillo-Marcos, Marta Casado-Pelaez, Veronica Davalos, Gerardo Ferrer, Caterina Mata, Elisabetta Mereu, David Valcarcel, Antonieta Molero, Lurdes Zamora, Laura Palomo, Pamela Acha, Ana Manzanares, Francesc Solé, Manel Esteller. Single-cell multiomics analysis of myelodysplastic syndrome predicts clinical response to DNA methylation inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB130.
Genome-wide CRISPR screening of chondrocyte maturation newly implicates genes in skeletal growth and height-associated GWAS loci
Authors: John M. Baronas, Eric Bartell, Anders Eliasen, John G. Doench, Loic Yengo, Sailaja Vedantam, Eirini Marouli, Henry M. Kronenberg, Joel N. Hirschhorn, Nora E. Renthal
Journal: Cell Genomics (2023)

Alterations in the growth and maturation of chondrocytes can lead to variation in human height, including monogenic disorders of skeletal growth. We aimed to identify genes and pathways relevant to human growth by pairing human height genome-wide association studies (GWASs) with genome-wide knockout (KO) screens of growth-plate chondrocyte proliferation and maturation